The enteric nervous system has been postulated to be involved in several gut functions such as motility, the enteric reflex and mucosal transport. Evidence for these functions is indirect because enteric neurons lie within the gut wall, making intrinsic nerve ablation difficult. We will employ surfactants, a group of nonspecific membrane perturbating substances, to selectively denervate the gut and to examine the associated alterations in GI functions. Preliminary studies indicate tht serosal application of the cationic surfactant benzalkonium chloride (BAC) to the rate jejunum selectively reduces the number of ganglion cells in the myenteric plexus. BAC also reduces the vasoactive intestinal peptide immunoreactivity mainly in the myenteric plexus, further demonstrating toxicity selective for neurons. We have examined electric parameters in BAC-treated out and found disruption of the basic electric rhythm (BER) and elimination of spiking activity, the electrical correlate to muscle contractions. Our results with BAC suggest a modulation of the BER and intestinal muscle contractions by myenteric neurons. In addition, sodium ricionleate, the active component of castor oil, also a surfactant, significantly reduces the ganglio cells in both the myenteric and submucosal plexuses. We propose to characterize this surfactant-induced intrinsic denervation of the gut and use this denervation technique to elucidate the role of the enteric neurons in GI motility and intestinal secretion/absorption. We will quantitatively evaluate the effect of denervation on smooth muscle viability, BER frequency, spike potentials and the propagation of the migrating myoelectric complex. In addition, pharmacological analysis will be performed employing drugs acting primarily on smooth muscle or enteric neurons, to test the viability of chronically denervated gut muscle. Finally, the mucosal activity of an intrinsically denervated gut will be studied alone and in response to agents which enhlance or inhibit intestinal absorption. Our studies are unique. They will clarify the role of the enteric nerves in normal gut function, serve as a model for congenital and acquired pathology, i.e., Hirschsprung's and Chagas diseases and may xplain why several pharmacological agents alter GI activity.